Camptothecin (“CPT”), shown below, is an indole alkaloid natural product isolated from the oriental tree Camptotheca acuminata, which has substantial anti-tumor activity in animal models. The compound has a pentacyclic ring system with an asymmetric center in ring E with a 20 S configuration. The pentacyclic ring system includes a pyrrolo [3, 4-b] quinoline (rings A, B and C), a conjugated pyridone ring D), and six membered lactone (ring E) with an 20α-hydroxyl group. 
Subsequent studies established that CPT inhibited both DNA and RNA synthesis. Recent research has demonstrated that CPT and CPT analogues interfere with the mechanism of action of the cellular enzyme topoisomerase I, which is important in a number of cellular processes (e.g., DNA replication and recombination, RNA transcription, chromosome decondensation, etc.).
A significant problem with CPT and CPT analogues is the chemical lability of the α-hydroxy lactone functionality. Rapid in situ hydrolysis of the α-hydroxy lactone provides a ring opened carboxylate form which is relatively inactive, as was shown in early clinical studies with CPT sodium.
One solution to the chemical instability of the α-hydroxy lactone group found in CPT is insertion of a carbon atom between the free hydroxy group and the carbonyl carbon of the lactone group to provide a ring expanded β-hydroxy lactone known as homo-Camptothecin (“hCPT”), which is shown below. hCPT is considerably more stable than CPT because of the reduced susceptibility of the lactone carbonyl to nucleophilic attack. Importantly, possesses substantial anti-proliferative activity in animal studies. 
Accordingly there is a need for new analogues of hCPT that may be stable anti-proliferative agents.